Effects of metapopulation structure and recombination on bacterial populations

Bacteria are subject to a wide variety of complementary and competing forces which work to shape the populations observed in the natural world. In the case of bacterial pathogens, epidemiological factors play a significant role in the evolution of a pathogenic species, and the relatively low diversities observed on a global scale in significant pathogens may be due to the phenomenon of a microepidemic population structure, operating in concert with homologous recombination and mutation. In this work I explicitly define the microepidemic population concept in population genetics terms, and examine its consequences for pathogen population structure and inference of population characteristics from data. I make use of simulated metapopulations to model simplified populations composed of neutral microepidemics in order to examine the varying effects of homologous recombination and mutation in pathogens. The analysis is then extended to include different kinds of selection, both at an individual level and at a metapopulation level, to investigate the consequences of these processes, and to contrast with the results from neutral populations. With the increasing number of resources containing large, globally sampled strain collections, I also examine the effects of metapopulation structure on population genetic methods of analysis which have been applied to bacterial datasets (including Gst, the Neutral Microepidemic Model, and IA). Using simulated populations I consider these methods in light of database limitations such as those arising from the longitudinally sampled nature of the collections, and those introduced by geographic over- and undersampling. This is followed by an examination of the effectiveness of some of the methods using sequence data (phylogenetics, BAPS and ClonalFrame) which are commonly employed to ask questions relating to population structure. The work concludes with the application of these methods to examine the population genetics of several bacteria of interest

Automated cloud brokerage based upon continuous real-time benchmarking

Over the last few years there has been a massive proliferation of cloud providers, all using a set of different metrics to describe the service solutions that they offer. This results in a lack of comparability within and between services that precludes end users being able to select the most appropriate service for their needs, based upon their requirements. Here we outline an automated real-time benchmarking platform that can interact with cloud brokers to automatically select the most optimal cloud service provider for a given workload, based upon up to the minute benchmarking results generated, stored, collated and compared by the platform itself. This software package could save end users and enterprises significant amounts of time and money by ensuring that they always use the most appropriate VM flavor, on the most appropriate cloud service, every time they run a workload

Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease

BACKGROUND: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sensorimotor disorder that causes patients to experience overwhelming and distressing sensations in the legs compelling the patient to move their legs to provide relief. The purpose of this study was to determine if biomarkers in the cerebrospinal fluid can distinguish RLS/WED patients from neurological controls. METHODS: We obtained CSF samples by lumbar puncture from 5 early-onset RLS/WED patients and 5 controls. We performed 2-dimensional difference in-gel electrophoresis (2D-DIGE). Proteins that were significantly altered were identified by Student’s t-test. Protein spots that were differentially expressed (p ≤ 0.05, Av. Ratio ≥ 2.0) between RLS/WED and control CSF samples were identified using MALDI-TOF-MS. Statistical analyses of the validation immunoblot assays were performed using Student’s t-test. RESULTS: In this discovery study we identified 6 candidate CSF protein markers for early-onset RLS/WED. Four proteins (Cystatin C, Lipocalin-type Prostaglandin D2 Synthase, Vitamin D binding Protein, and β-Hemoglobin) were increased and 2 proteins (Apolipoprotein A1 and α-1-acid Glycoprotein) were decreased in RLS/WED patients. CONCLUSIONS: Our results reveal a protein profile in the RLS/WED CSF that is consistent with clinical findings of disruptive sleep, cardiovascular dysfunction and painful symptoms. Moreover, protein profiles are consistent with neuropathological findings of activation of hypoxia inducible factor (HIF) pathways and alterations in dopaminergic systems. These data indicate the CSF of RLS/WED patients may provide information relevant to biological basis for RLS/WED, treatment strategies and potential new treatment targets

Use of whole-genus genome sequence data to develop a multilocus sequence typing tool that accurately identifies Yersinia isolates to the species and subspecies levels

The genus Yersinia is a large and diverse bacterial genus consisting of human-pathogenic species, a fish-pathogenic species, and a large number of environmental species. Recently, the phylogenetic and population structure of the entire genus was elucidated through the genome sequence data of 241 strains encompassing every known species in the genus. Here we report the mining of this enormous data set to create a multilocus sequence typing-based scheme that can identify Yersinia strains to the species level to a level of resolution equal to that for whole-genome sequencing. Our assay is designed to be able to accurately subtype the important human-pathogenic species Yersinia enterocolitica to whole-genome resolution levels. We also report the validation of the scheme on 386 strains from reference laboratory collections across Europe. We propose that the scheme is an important molecular typing system to allow accurate and reproducible identification of Yersinia isolates to the species level, a process often inconsistent in nonspecialist laboratories. Additionally, our assay is the most phylogenetically informative typing scheme available for Y. enterocolitica

Modelling scour around submerged objects with TELEMAC3D - GAIA

Hydrodynamic

Atomistic simulations of α - Fe /Nd2Fe14B magnetic core/shell nanocomposites with enhanced energy product for high temperature permanent magnet applications

Nd 2 Fe 14 B has generated significant interest since its discovery in the 1980s due to its impressive energy density, which makes it a prime candidate for use in permanent magnet applications. Its performance is known to suffer greatly at the high temperatures required for motor applications around 450 K. Core/shell nanocomposites provide a potential route to improve material performance by combining the highly anisotropic permanent magnet with a material with high moment and high Curie temperature. We have used an atomistic spin model to investigate the magnetic properties of Nd 2 Fe 14 B with α - F e in a core/shell nanostructure. We find that at typical motor operating temperatures, increasing α - F e content reduces the coercivity of the system while enhancing the saturation magnetization. The overall effect is that an improvement in B H max is seen with increasing α - F e up to an optimal value of 70 vol. %. This property of core/shell nanostructures would make them a suitable substitute for pure Nd 2 Fe 14 B while simultaneously lowering the raw material cost of the permanent magnet component of high-performance motors

Retrospective Analysis of Serotype Switching of Vibrio cholerae O1 in a Cholera Endemic Region Shows It Is a Non-random Process.

Genomic data generated from clinical Vibrio cholerae O1 isolates collected over a five year period in an area of Kolkata, India with seasonal cholera outbreaks allowed a detailed genetic analysis of serotype switching that occurred from Ogawa to Inaba and back to Ogawa. The change from Ogawa to Inaba resulted from mutational disruption of the methyltransferase encoded by the wbeT gene. Re-emergence of the Ogawa serotype was found to result either from expansion of an already existing Ogawa clade or reversion of the mutation in an Inaba clade. Our data suggests that such transitions are not random events but rather driven by as yet unidentified selection mechanisms based on differences in the structure of the O1 antigen or in the serotype-determining wbeT gene

The type III secretion system effector SeoC of salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and inhibits opsonophagocytosis

Salmonella species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella enterica subsp. salamae strain 3588/07 against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and Salmonella bongori strain 12419. S. enterica subsp. salamae encodes the Salmonella pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. enterica subsp. salamae invades HeLa cells and contains homologues of S. bongori sboK and sboC, which we named seoC SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonella isolates, we identified EspJ homologues in S. bongori, S. enterica subsp. salamae, and Salmonella enterica subsp. arizonae The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the Salmonella SeoC/SboC homologues ADP-ribosylate Src E310 in vitro Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. enterica subsp. salamae infection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. enterica subsp. salamae, and S. enterica subsp. arizonae share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae